The protein level and transcription activity of activating transcription factor 1 is regulated by prolyl isomerase Pin1 in nasopharyngeal carcinoma progression
| Autor: | Zhiwei He, Ying Zou, Takafumi Uchida, Jian Wang, Hua Chen, Zhu Zhu, Liyong Chen, Weilong Liu, Zigang Dong, Tong Li, Binbin Li, Guo Liang Huang, Caiguo Ye, Dan Liao, Yan Lu, Huahui Li |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Threonine Cancer Research Transcription Genetic Carcinogenesis Immunology Mice Nude Biology medicine.disease_cause 03 medical and health sciences Cellular and Molecular Neuroscience Transcription (biology) Cell Line Tumor medicine Prolyl isomerase Animals Humans Phosphorylation Regulation of gene expression Activating Transcription Factor 1 Mice Inbred BALB C Nasopharyngeal Carcinoma ATF1 Protein Stability Carcinoma Nasopharyngeal Neoplasms Cell Biology medicine.disease Gene Expression Regulation Neoplastic NIMA-Interacting Peptidylprolyl Isomerase 030104 developmental biology HEK293 Cells Nasopharyngeal carcinoma Mutation Cancer research PIN1 Disease Progression Tumor promotion Original Article Protein Binding |
| Zdroj: | Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | The function of activating transcription factor 1 (ATF1) and the mechanism about why ATF1 was over-phosphorylated in nasopharyngeal carcinoma (NPC) progression is completely undiscovered. In this study, a series of experiments both in vitro and in vivo were used to characterize a promotive function of ATF1 in NPC tumorigenesis and identify prolyl isomerase Pin1 as a novel regulator of ATF1 at post-transcription. First, we found that overexpression of ATF1 promoted colony formation in NPC. However, the high protein level of ATF1 in NPC was not resulted from high mRNA level. Then, a direct interaction between Pin1 and ATF1 at Thr184 was demonstrated using mammalian two-hybrid assay and coimmunoprecipitation. Cycloheximide (CHX) treatment indicated Pin1 stabilized the expression of ATF1 at post-transcription level. We confirmed that Pin1 upregulated ATF1 transcriptional activity of Bcl-2 using luciferase reporter assay, quantitative RT-PCR and western blot. Furthermore, the newly identified phosphorylation of ATF1 at Thr184 was suggested to have an important role in ATF1 function of transcription and tumor promotion. Finally, high expression of Pin1 in NPC tissue was found to be positively correlated with ATF1. The ATF1 promoted NPC tumorigenesis was regulated by Pin1 both in vitro and in vivo. All these findings clearly state that Pin1 is a novel regulator of ATF1 at Thr184 and thereby enhances ATF1 transcription activity and tumorigenesis promotive function in NPC. |
| Databáze: | OpenAIRE |
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